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Trial record 32 of 49 for:    nadide

Nicotinamide Riboside in LVAD Recipients (PilotNR-LVAD)

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ClinicalTrials.gov Identifier: NCT03727646
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : November 1, 2018
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Kevin O'Brien, University of Washington

Brief Summary:
While preliminary data show that oral nicotinamide riboside (NR) supplementation increases myocardial levels of oxidized nicotine-adenine dinucleotide (NAD+) levels in mice, there has been no direct evidence that suggests oral NR increases NAD+ levels or improves mitochondrial function in human hearts. This Pilot Study is designed to obtain feasibility data for a planned, larger study testing the hypothesis that oral NR supplementation will increase myocardial NAD+ levels and improve cardiomyocyte mitochondrial function in participants with advanced heart failure planned for elective left ventricular assist device (LVAD) implantation. To demonstrate safety and feasibility of NR in this patient population, the investigators propose to enroll 5 participants planned for LVAD implantation in a Pilot Study of NR in which participants will receive NR, up-titrated over 3 days to a final NR dose of 1000mg twice daily. Blood and myocardial tissue analyses collected previously from age- and gender-matched LVAD recipients will serve as controls.

Condition or disease Intervention/treatment Phase
Heart Failure,Congestive Heart Failure New York Heart Association Class IV Mitochondrial Alteration Dietary Supplement: Nicotinamide riboside Early Phase 1

Detailed Description:

This Pilot Study will examine the following Aims:

Aim 1: Enroll 5 participants scheduled for elective left ventricular assist device (LVAD) placement into an open-label study of nicotinamide riboside (NR).

a. Participants will have labs (including safety panels) drawn at baseline (Day 1), then receive escalating doses of NR to a maximum dose of 1000mg twice daily by Day 3. Participants will be continued on NR at 1000mg twice daily until LVAD implantation surgery.

On the morning of LVAD implantation Surgery (Day 5 or later), participants will have final labs drawn. Samples of fresh cardiac tissue removed from the left ventricular apex during LVAD implantation surgery will be collected in the operating room. The primary analyses will be performed on NR-treated participants who were on the maximum NR dose of 1000mg twice daily for at least 2 days prior to LVAD implantation surgery. The maximum duration of NR administration will be capped at 14 days. If the surgery doesn't happen by then, the participant will be withdrawn from the study.

Aim 2: Determine the effect of NR (as compared to historical controls) on levels of the oxidized and reduced forms of nicotine-adenine dinucleotide (NAD+ and NADH, respectively), mitochondrial function and its regulation through modifications of the epigenome in the failing myocardium.

  1. Measure NAD+ and NADH levels in the blood and myocardium of the participants.
  2. Assess mitochondrial morphology and function in cardiac tissue using, respectively, electron microscopy (EM) and isolated mitochondria.
  3. Determine protein acetylation in the mitochondrial and non-mitochondrial compartments and changes in nuclear gene regulation.

Aim 3: Test the hypothesis that NR improves mitochondrial function and reduces inflammatory response in heart failure (HF) patients receiving NR (as compared to historical controls).

  1. Measure mitochondrial function in peripheral blood mononucleated cells (PBMC).
  2. Determine the inflammatory response in PBMC.
  3. Compare effects on the circulating inflammasome vs. myocardial inflammation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This single-center, open-label study will compare blood and myocardial NAD+ levels and other mitochondrial endpoints in participants with end-stage heart failure treated with open-label nicotinamide riboside prior to LVAD implantation to similar endpoints from untreated patients previously undergoing LVAD implantation.
Masking: Single (Outcomes Assessor)
Masking Description: Study biostatistician will be blinded to group (NR vs. untreated controls)
Primary Purpose: Treatment
Official Title: Pilot Study of Preoperative Nicotinamide Riboside (Vitamin B3) Supplementation in Patients Undergoing Elective Left Ventricular Assist Device (LVAD) Implantation
Actual Study Start Date : September 26, 2018
Estimated Primary Completion Date : February 26, 2019
Estimated Study Completion Date : July 26, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Open-label nicotinamide riboside

Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:

Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)

Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily

Washout Day of LVAD Surgery and/or Day 15: None

Dietary Supplement: Nicotinamide riboside
nicotinamide riboside supplied as 250mg capsules

No Intervention: Baseline controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.



Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 14 days ]
    Adverse Events


Secondary Outcome Measures :
  1. Effect of NR on whole blood NAD+ levels [ Time Frame: Duration of NR treatment ]
    Change in whole blood NAD+ levels from Baseline to Day of Surgery in NR-treated participants

  2. Effect of NR on mitochondrial respiration (Seahorse assay) in isolated peripheral blood mononuclear cells (PBMCs) [ Time Frame: Up to 14 days ]
    Change in mitochondrial respiration from Baseline to Day of Surgery in NR-treated participants

  3. Between-group comparison of whole blood NAD+ levels [ Time Frame: Up to 14 days ]
    Comparison of whole blood NAD+ levels on the Day of LVAD Surgery in NR-treated vs. historical control patients

  4. Between-group comparison of mitochondrial respiration in PBMCs [ Time Frame: Up to 14 days ]
    Comparison of mitochondrial respiration in PBMCs on the Day of LVAD Surgery in NR-treated vs. historical control patients



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of advanced heart failure.
  • Planned elective LVAD implantation surgery with patient agreements for candidacy in place as required by UWMC.
  • Hospital inpatient at time of enrollment.
  • Ability to undergo Study procedures.
  • Willingness/ability to provide informed consent.

Exclusion Criteria:

  • Current smoking
  • Receiving certain concurrent supplements (to be determined at discretion of the PI). Note that UWMC Nutrition Care standards call for a general multivitamin (1 tab PO daily) as part of the advanced heart failure therapy (AHFT) work-up.
  • Known allergies to niacin or nicotinamide.
  • Hepatic, renal, endocrine, or neurological disease that disqualify them from consideration for LVAD implantation.
  • Inability to perform Study visits or procedures.
  • Unwillingness/inability to provide informed consent.
  • Women who are currently pregnant or who wish to become pregnant over the course of the study follow-up are not allowed to join this study. This exclusion is built into the LVAD candidate selection process.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727646


Contacts
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Contact: Laura McMartin 206-616-5910 mcmartin@uw.edu
Contact: Fatemeh Ranjbaran 206-221-9154 fatimar@uw.edu

Locations
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United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Kevin D O'Brien, MD    206-529-7802    cardiac@uw.edu   
Contact: Rong Tian, MD    206 616-5672    rongtian@u.washington.edu   
Sponsors and Collaborators
University of Washington
American Heart Association
Investigators
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Principal Investigator: Kevin O'Brien, MD University of Washington

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Responsible Party: Kevin O'Brien, Professor, School of Medicine: Department of Medicine: Cardiology: Clinical, University of Washington
ClinicalTrials.gov Identifier: NCT03727646     History of Changes
Other Study ID Numbers: STUDY00005431
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents